Longitudinal Trajectories of Informant-Reported Daily Functioning in Empirically Defined Subtypes of Mild Cognitive Impairment

Objectives: Within the Alzheimer's Disease Neuroimaging Initiative (ADNI)'s mild cognitive impairment (MCI) cohort, we previously identified MCI subtypes as well as participants initially diagnosed with MCI but found to have normal neuropsychological, biomarker, and neuroimaging profiles. We investigated the functional change over time in these empirically derived MCI subgroups. Methods: ADNI MCI participants (n=654) were classified using cluster analysis as Amnestic MCI (single-domain memory impairment), Dysnomic MCI (memory+language impairments), Dysexecutive/Mixed MCI (memory+language+attention/executive impairments), or Cluster-Derived Normal (CDN). Robust normal control participants (NCs; n=284) were also examined. The Functional Activities Questionnaire (FAQ) was administered at baseline through 48-month follow-up. Multilevel modeling examined FAQ trajectories by cognitive subgroup. Results: The Dysexecutive/Mixed group demonstrated the fastest rate of decline across all groups. Amnestic and Dysnomic groups showed steeper rates of decline than CDNs. While CDNs had more functional difficulty than NCs across visits, both groups' mean FAQ scores remained below its suggested cutoff at all visits. Conclusions: Results (a) show the importance of executive dysfunction in the context of other impaired cognitive domains when predicting functional decline in at-risk elders, and (b) support our previous work demonstrating that ADNI's MCI criteria may have resulted in false-positive MCI diagnoses, given the CDN's better FAQ trajectory than those of the cognitively impaired MCI groups.